• Login
    • Join
  • FOLLOW:
  • Subscribe Free
    • Magazine
    • eNewsletter
    Checkout
    • Magazine
    • News
    • Manufacturing
    • Packaging
    • Development
    • Compliance
    • Top 25
    • Directory
    • Microsites
    • Events
    • More
  • Magazine
  • News
  • Manufacturing
  • Packaging
  • Development
  • Compliance
  • Top 25
  • Directory
  • Microsites
  • Events
  • Current / Back Issue
    Features
    Editorial
    Columns
    Digital Edition
    eNewsletter Archive
    Our Team
    Editorial Guidelines
    Subscribe Now
    Advertise Now
    Top Features
    Small Innovators & Niche CROs

    Focus on Science

    Rapid and Data Rich Chromatographic Method Development

    Preparing Your Post Pandemic Talent Strategy

    How Modern Near-Infrared Came to Be
    Breaking News
    Online Exclusives
    Industry News
    Collaborations & Alliances
    Promotions & Moves
    Trials & Filings
    Financial Reports
    Bio News & Views
    Custom Sourcing News
    Packaging & Tracking
    CRO News
    Live From Shows
    Top News
    Bristol Myers Squibb Expands at Cambridge Crossing

    Amgen Completes Five Prime Acquisition

    Sartorius Expands in the UK

    Obituary Notice: Russell “Russ” Haines

    Abenza Chooses North Carolina for New Biologics Manufacturing Site
    APIs
    Aseptic Processing
    Cleaning Validation
    Clinical Trial Materials
    Cytotoxics and High Potency Manufacturing
    Equipment
    Excipients
    Extractables and Leachables
    Facilities
    Fill/Finish
    Lyophilization
    Parenterals
    Process Development
    Process Validation
    Risk Management
    Scale-up/ Technology Transfer
    Solid Dosage/ Creams/ Ointments

    Abenza Chooses North Carolina for New Biologics Manufacturing Site

    Catalent Adds Cryogenic Capabilities at Philadelphia Facility

    Recro, Ensysce Expand Development and Manufacturing Partnership

    Metrics Names Stephanie Emory Associate Director of Pharma Development

    Albumedix Completes Commercial-Scale Mfg. Facility Expansion
    Capsules
    Cold Chain Management
    Injectables
    Logistics
    Serialization
    Solid Dosage / Semi-solids
    Supply Chain
    Vials

    Obituary Notice: Russell “Russ” Haines

    Catalent Adds Cryogenic Capabilities at Philadelphia Facility

    Cryoport Acquires Critical Transport Solutions Australia

    PharmParts – This Makes Sense!

    Securing Your API Supply Chain: Three Keys to Success
    Analytical Services
    Bioanalytical Services
    Bioassay Developement
    Biologics, Proteins, Vaccines
    Biosimilars
    Chemistry
    Clinical Trials
    Drug Delivery
    Drug Development
    Drug Discovery
    Formulation Development
    Information Technology
    Laboratory Testing
    Methods Development
    Microbiology
    Preclinical Outsourcing
    R&D
    Toxicology

    Bristol Myers Squibb Expands at Cambridge Crossing

    Amgen Completes Five Prime Acquisition

    Sartorius Expands in the UK

    Abenza Chooses North Carolina for New Biologics Manufacturing Site

    Arkema Recruits Dotmatics as its R&D Digitalization Partner
    Filtration & Purification
    GMPs/GCPs
    Inspections
    QA/QC
    Regulatory Affairs
    Validation

    Ensuring Pharma Manufacturing Quality

    What Will Change at FDA for 2021?

    RBQM Comes of Age: COVID as a Catalyst for Change

    Post-Pandemic Regulations

    Enteris BioPharma: Custom Solutions – From Bench to Market
    Companies
    Categories
    Corporate Capabilities
    Add New Company
    Contract Service Directory Companies
    Almac Group

    PCI Pharma Services

    Adare Pharma Solutions

    Baxter BioPharma Solutions

    Reed-Lane
    Companies
    News Releases
    Posters
    Brochures
    Services
    Videos
    Case Study
    White Papers
    Jobs
    Contract Service Directory Companies
    Syngene

    Alcami

    Reed-Lane

    Baxter BioPharma Solutions

    Emergent BioSolutions
    Webinars
    Live From Shows
    • Magazine
      • Current / Back Issue
      • Features
      • Editorial
      • Columns
      • Editorial Guidelines
      • Subscribe Now
      • Advertise Now
      • Enewsletter Archive
      • Digital Edition
    • Directory
      • Companies
      • Categories
      • Corporate Capabilities
      • Add Your Company
    • Manufacturing
      • APIs
      • Aseptic Processing
      • Cleaning Validation
      • Clinical Trial Materials
      • Cytotoxics and High Potency Manufacturing
      • Equipment
      • Excipients
      • Extractables and Leachables
      • Facilities
      • Fill/Finish
      • Lyophilization
      • Parenterals
      • Process Development
      • Process Validation
      • Risk Management
      • Scale-up/ Technology Transfer
      • Solid Dosage/ Creams/ Ointments
      • cGMP Manufacture
    • Packaging
      • Capsules
      • Cold Chain Management
      • Injectables
      • Logistics
      • Serialization
      • Solid Dosage / Semi-solids
      • Supply Chain
      • Vials
    • Development
      • Analytical Services
      • Bioanalytical Services
      • Bioassay Developement
      • Biologics, Proteins, Vaccines
      • Biosimilars
      • Chemistry
      • Clinical Trials
      • Drug Delivery
      • Drug Development
      • Drug Discovery
      • Formulation Development
      • Information Technology
      • Laboratory Testing
      • Methods Development
      • Microbiology
      • Preclinical Outsourcing
      • R&D
      • Toxicology
    • Compliance
      • Filtration & Purification
      • GMPs/GCPs
      • Inspections
      • QA/QC
      • Regulatory Affairs
      • Validation
    • Top 25 Pharma & BioPharma
    • Contract Pharma Direct
    • Breaking News
    • Online Exclusives
    • Slideshows
    • Experts Opinions
    • Surveys
      • Outsourcing Survey
      • Salary Survey
    • Glossary
    • Videos
    • Podcasts
    • White Papers
    • Infographics
    • Contract Pharma Conference
      • Contract Pharma Conference
      • Speakers
      • Exhibitors
      • Conference Sessions
    • Supplier Microsite
      • Companies
      • News Releases
      • Posters
      • Brochures
      • Services
      • Videos
      • Case Study
      • White Papers
    • eBook
    • Webinars
    • Events
      • Industry Events
      • Live from Show Events
      • Webinars
    • Classifieds / Job Bank
      • Classifieds
      • Job Bank
    • About Us
      • About Us
      • Contact Us
      • Advertise With Us
      • Privacy Policy
      • Terms of Use
    Features

    Handling & Assessing HPAPIs

    As oncology pipelines grow, so too is the demand for highly potent materials, which require careful handling and containment.

    Handling & Assessing HPAPIs
    Related CONTENT
    • Vetio Animal Health
    • Quality Metrics Feedback
    • Changing the Face of CDMOs
    • Drug Substances: Scale-Up Challenges
    • API to ADC: A Journey Through High Potency
    Jason Korbel, Technical Services Manager, Cambrex Charles City09.16.19
    The containment and handling precautions that are required when manufacturing active pharmaceutical ingredients (APIs) and their intermediates vary according to the hazards posed by the individual materials. Clearly, those that pose greater risk to human health must be handled much more cautiously than those that are less likely to cause problems. A current trend in the small molecule API market is the growth of the oncology pipeline, which is at about twice that of other indications, and various market data suggest as being between 30 and 40 percent of preclinical and clinical small molecules. Because of the clinical data available about developmental compounds, many oncology drugs are classed as “highly potent” and although by no means is this the only therapeutic class of compounds that are classified as such, these highly potent molecules require careful handling and specific containment facilities.

    Handling and assessment of highly potent materials
    Handling chemicals considered hazardous is more time-consuming and expensive than working with those that are not, and for contract development and manufacturing organizations (CDMOs),  simply treating every project as if it were highly dangerous is not appropriate. Instead, to ensure projects can be managed cost-effectively, a careful risk assessment should be carried out before any API manufacturing project is embarked upon.

    The risk assessment weighs all of the information that is available, both about the API itself, and any raw materials or intermediates that are used in its manufacture, and this is particularly important for highly potent APIs (HPAPIs). Where there is a paucity of information at the outset for development compounds and scale-up projects, the risk assessment will take on board whatever data are available, and use it to determine an exposure limit that is likely to be safe for the operators, and the containment that will be required. However, the risk of being overly conservative and imposing far more controls than are truly needed can cause costs to escalate, so needs to be avoided whenever possible.

    Different companies use their own classification systems in which the numbers of compound classes and their criteria vary, and at Cambrex we use a five category exposure control band (ECB) system to determine the handling requirements. ECB 1 includes chemicals that have a relatively high occupational exposure limit above 100 µg/m3. In ECB 2, the products will have exposure ranges at a level of 10–100 µg/m3. Containment will be required for these materials, but local ventilation will typically suffice, and open handling will remain acceptable. 

    Those compounds that fall into ECB 3 and ECB 4 have substantially higher risk levels, and HPAPIs will always be placed in one of these categories. For ECB3, where the allowable exposure limit is 1–10 µg/m3, containment with no open handling will be necessary. If it falls into ECB 4, where the allowable exposure limit is 0.1-1µg/m3, full containment in an isolator will be essential.  Although very small quantities of ECB 3 and ECB 4 may be handled outside of containment in certain situations.

    The greatest level of risk is posed by those chemicals that we place in ECB 4+ with allowable exposure limits at 0.01-0.1 µg/m3. No open handling whatsoever of such materials is permitted, even if they are in solution, and they must remain within barrier isolation at all times. This group will include products such as API warheads for antibody–drug conjugates.

    There is also an additional sub-category. ECB 2* will include any compound that otherwise sits in ECB 1 or ECB 2 because of its toxicity levels, but which has a special hazard associated with it. It might be a mutagen, carcinogen, sensitizer, or a chemical that poses developmental or reproductive risks. It might also be prone to dermal absorption, pose an inhalation hazard, or have an adrenergic effect. In these cases, additional training, and physical or administrative controls, will be required.

    The project safety dossier
    The risk assessment is used to inform the creation of a project safety dossier (PSD) for each product. This will include every chemical substance involved in the process, other than common reagents, catalysts and solvents. It will provide the chemist or operator with occupational exposure bands (OEBs), and the rationale behind their determination. It is important to include the reasoning behind the classification because it will give workers an insight into the reasoning behind the handling requirements, and therefore increase buy-in within the whole project team.

    Importantly, the PSD will also include presumptive or demonstrated destruction procedures for any ECB 3, ECB 4, or ECB 4+ chemicals. Presumptive procedures are acceptable for development activities, while demonstrated procedures will be required before the project moves into pilot and commercial manufacturing. 

    The dossier will identify special hazards and especially hazardous reagents. Administrative controls and personal protective equipment (PPE) will be provided, along with ECB procedures.

    The PSD uses a color-coded procedure on the front page for ease of identification, and this front page will be affixed to the door of the lab or suite where the product is being handled. In a multi-purpose facility where projects are undertaken for multiple different customers, this color-coding highlights hazards without disclosing any confidential client or chemical structure information.

    The second part of the dossier is a single page that highlights the top-line hazard information, including chemical-specific information. Part 3 includes more detailed information, such as chemical structures of all raw materials, intermediates and final products, along with their OEB range, and ECB control procedures.

    In part 4, the detailed information from the chemical-by-chemical risk assessment is laid out. This is where we feel Cambrex differentiates itself, including the justification for each chemical’s OEB rating and ECB strategy in a fashion that is easily understood by all coworkers all the way to the operator level to achieve buy-in. Coworkers end up with a high level of respect for the chemicals they are handling and the controls/procedures to keep them safe. Finally, in part 5, there will be a list of references.

    For high ECB category projects, employee training takes place as the scale of manufacture increases to ensure operators and chemists are aware of specific risks prior to working with the materials. It is valuable to involve toxicology specialists in training sessions to allow discussions to take place and for affected employees to raise any queries, or clarify any specific protocols.

    Building and designing a containment facility
    For CDMOs looking to design a multipurpose facility, there are a number of challenges in the process. Cambrex has just completed the building of a HPAPI manufacturing facility at its site in Charles City, Iowa. Reviewing the project highlights the following considerations were taken into account in the design and construction:

    1. Cross functional design team
    The project design team should be set up to ensure that existing knowledge about HPAPIs of both internal experts and external partners are leveraged. These should include project engineers, maintenance, equipment vendors, experienced operators, and representatives from environmental health and safety (EH&S) and operations functions, as well as engineering design specialists, and the general building contractor.

    The design team can then develop the equipment sizing, the layout of the facility and the equipment within it, as well as the unit operation capability, based on both prior API experience and customer input. Engineering partners can assist in ensuring that the building codes and regulatory requirements – which are constantly evolving – are met, and can offer up-to-date information and experience about these.

    2. Future needs
    For a CDMO, a facility is built on specifications and matches the needs of current demands, with no knowledge of what will be made within it in coming years. Substantial assumptions about the future capability needs have to be made, informed by past experience. Projections about previous requirements and demands against actual experience can ensure that a facility does not become obsolete or in need of further expansion as soon as it is completed.

    3. Scale and Containment Capabilities
    Understanding the market influences the design criteria for a facility.  Considering the target batch size for materials being manufactured is important as this affects the level of containment that is economic to achieve. To have appropriate containment below an OEL of 0.1 µg/m3 becomes very difficult and expensive to achieve, particularly for the mid-scale to large batch sizes (100-300 kg). Few batches this large are likely to be so potent that they are below that OEL, because such minuscule doses are required that no more than a few kg may ever need to be made.

    As with any plant design, the target batch size dictates the equipment size such as filters for isolation steps. Reactor choice is influenced by the types of chemistries being performed, and the concentrations needed – so it may be that various sizes and material of construction (Glass Lined / Hastelloy) are considered.

    4. Isolator technology
    In terms of the isolator technology, there are advantages and disadvantages for both rigid and flexible alternatives. With a fixed or rigid isolator, the capital cost will be high, there will be a long lead time, and it will be difficult to modify for different operations, but the operating costs could be lower and it will generally be more robust and easier for the operators to manipulate. In contrast, flexible containment or isolator alternatives will have a lower initial cost and shorter lead time, but operating costs might be higher and more delicate operator technique will be necessary. Furthermore, no modifications are possible; any changes must be made by purchasing a different item from the vendor.

    It may be appropriate to have a mixed approach, depending on the needs of the facility and assumptions about volumes being handled. If the end product is likely to be low OEL and high volume, a fixed isolator may be appropriate for final product packaging and sampling, with a flexible approach for material charging that can handle a wide variety of OELs, volumes, reactor destinations and methods.

    There are more drugs and therapies being developed and coming to the market that are classified as “highly potent,” as well as a number of commercial products reaching patent expiry. For CDMOs wishing to capitalize on this market opportunity, having appropriate assets to manufacture the molecules effectively and efficiently is crucial, as is the level of expertise to handle the projects safely. 
    Related Searches
    • Manufacturing
    • training
    • isolation
    • API
    Suggested For You
    Vetio Animal Health Vetio Animal Health
    Quality Metrics Feedback Quality Metrics Feedback
    Changing the Face of CDMOs Changing the Face of CDMOs
    Drug Substances: Scale-Up Challenges Drug Substances: Scale-Up Challenges
    API to ADC: A Journey Through High Potency API to ADC: A Journey Through High Potency
    Preparing for Your CDMO Selection Process Preparing for Your CDMO Selection Process
    GenCure Reports Successful First Run of 80L Bioreactor GenCure Reports Successful First Run of 80L Bioreactor
    Cambrex Makes Senior Appointments Cambrex Makes Senior Appointments
    Catching Up With Cambrex Catching Up With Cambrex
    The Modern CDMO The Modern CDMO
    Cambrex Opens QC Lab in Italy Cambrex Opens QC Lab in Italy
    Cambrex Completes Highly Potent API Mfg. Site Cambrex Completes Highly Potent API Mfg. Site
    WuXi Biologics, NBE-Therapeutics Enter ADC Devt. and Mfg. Tie-up WuXi Biologics, NBE-Therapeutics Enter ADC Devt. and Mfg. Tie-up
    Technical Advantages of Continuous Flow Chemical Synthesis Technical Advantages of Continuous Flow Chemical Synthesis
    CEO Spotlight: Salim Haffar CEO Spotlight: Salim Haffar

    Related Features

    • R&D
      Small Innovators & Niche CROs

      Small Innovators & Niche CROs

      Smaller CROs have the opportunity to provide a niche approach to its clients, particularly smaller sponsors who have shared synergies.
      Neil Goodman, David Bruce and Mohamed El Malt, Europital 04.01.21

    • Laboratory Testing
      Focus on Science

      Focus on Science

      How to maximize lab performance and value through comprehensive equipment management.
      Rohit Shroff, Senior Vice President, Global Lab Products, Avantor 04.01.21

    • Analytical Services | Bioanalytical Services | Laboratory Testing | R&D
      Rapid and Data Rich Chromatographic Method Development

      Rapid and Data Rich Chromatographic Method Development

      An overview of what to consider when developing chromatographic methods.
      Daniel Kirschner, Executive Director of Analytical Services, Cambrex - Durham, North Carolina 04.01.21


    • Preparing Your Post Pandemic Talent Strategy

      Preparing Your Post Pandemic Talent Strategy

      Areas for consideration for adopting the right approach to reinforce investments, optimize business and maximize your workforce.
      Neil Kelly, Managing Partner, Vector Partners 04.01.21

    • Laboratory Testing | R&D
      How Modern Near-Infrared Came to Be

      How Modern Near-Infrared Came to Be

      First region outside the visible to be discovered and last to be utilized.
      Gary E. Ritchie, Contributing Writer 04.01.21

    • APIs | Supply Chain
      Securing Your API Supply Chain: Three Keys to Success

      Securing Your API Supply Chain: Three Keys to Success

      Key considerations when outsourcing API procurement and supply chain management.
      Selwyn Lustman and Lina Cogan, LGM Pharma 04.01.21


    • Solid Dosage/Semi-solids
      Hygienic Packaging Technology

      Hygienic Packaging Technology

      Growing consumer demand for health products highlights hygienic packaging.
      John Brown, Vice President of Global Marketing, Selig 03.01.21

    • Drug Delivery | Solid Dosage/Creams/Ointments
      Trends in Solid Oral Dosage Delivery

      Trends in Solid Oral Dosage Delivery

      Capsule demand continues to rise due to this delivery system’s versatility.
      Anita Solanki, Milind Biyani and Jnanadeva Bhat, PhD , ACG Capsules 03.01.21

    • Information Technology
      5 Reasons Paper Has No Place in Contract Manufacturing

      5 Reasons Paper Has No Place in Contract Manufacturing

      Digital solutions create more efficient manufacturing processes and eliminate delays.
      Dave Edwards, Chief Revenue Officer, MasterControl 03.01.21


    • Drug Delivery | Parenterals
      Injectable Drug Delivery Trends

      Injectable Drug Delivery Trends

      How medication trends are driving the shift to patient-friendly drug delivery systems.
      Peter Soelkner, Managing Director, Vetter 03.01.21

    • Pharmaceutical Manufacturing  Equipment Trends

      Pharmaceutical Manufacturing Equipment Trends

      Demand for flexibility remains the driving force behind equipment systems.
      Kristin Brooks, Managing Editor, Contract Pharma 03.01.21

    • Drug Delivery | Solid Dosage/Creams/Ointments
      Oral Solids:   Market & Technology Trends

      Oral Solids: Market & Technology Trends

      Oral solids remain the preferred route of drug delivery due to their cost-effectiveness, ease of manufacturing, and patient-friendly dose form options.
      Tim Wright, Editor, Contract Pharma 03.01.21


    • Nutraceutical Manufacturing:  Meeting the Challenges of Today, Planning for  Tomorrow

      Nutraceutical Manufacturing: Meeting the Challenges of Today, Planning for Tomorrow

      Companies continue balancing high demand, supply disruption, and worker safety during the pandemic.
      Sean Moloughney, Editor, Nutraceuticals World 03.01.21

    • 2021 Contract  Manufacturing Survey

      2021 Contract Manufacturing Survey

      Our fourth annual audience poll indicates continued reliance on manufacturing partners, particularly for small businesses.
      Sean Moloughney, Editor, Nutraceuticals World 03.01.21

    • APIs
      Small Molecule Development Trends

      Small Molecule Development Trends

      A Q&A with Cambrex Edinburgh’s site director, Mark Benger.
      Tim Wright, Editor, Contract Pharma 03.01.21

    Trending
    • Thermo Fisher Acquires PPD For $17.4B
    • Ensuring Pharma Manufacturing Quality
    • Bristol Myers Squibb Expands At Cambridge Crossing
    • Abenza Chooses North Carolina For New Biologics Manufacturing Site
    • Amgen Completes Five Prime Acquisition
    Breaking News
    • Bristol Myers Squibb Expands at Cambridge Crossing
    • Amgen Completes Five Prime Acquisition
    • Sartorius Expands in the UK
    • Obituary Notice: Russell “Russ” Haines
    • Abenza Chooses North Carolina for New Biologics Manufacturing Site
    View Breaking News >
    CURRENT ISSUE

    April 2021

    • Small Innovators & Niche CROs
    • Focus on Science
    • Rapid and Data Rich Chromatographic Method Development
    • Preparing Your Post Pandemic Talent Strategy
    • How Modern Near-Infrared Came to Be
    • Securing Your API Supply Chain: Three Keys to Success
    • View More >

    Cookies help us to provide you with an excellent service. By using our website, you declare yourself in agreement with our use of cookies.
    You can obtain detailed information about the use of cookies on our website by clicking on "More information”.

    • About Us
    • Privacy Policy
    • Terms And Conditions
    • Contact Us

    follow us

    Subscribe
    Nutraceuticals World

    Latest Breaking News From Nutraceuticals World

    AstaReal Astaxanthin Ingredient Receives U.S. Patent Approval
    Study on Kemin’s DailyZz Botanical Blend Uncovers Sleep Quality, Next-Day Performance Benefits
    FDA’s Dr. Cara Welch Opening Speaker at the 9th AHPA Botanical Congress
    Coatings World

    Latest Breaking News From Coatings World

    Jebsen & Jessen, Innospec Sign Distribution Agreement
    IGL Coatings Announces Partnership in Finland
    Axalta Schedules 1Q 2021 Earnings Conference Call
    Medical Product Outsourcing

    Latest Breaking News From Medical Product Outsourcing

    Iterative Scopes Announces IBD-Focused Scientific Advisory Board
    Vicarious Surgical, D8 Holdings Corp. Combine Operations in $1.1 Billion Deal
    FDA Grants De Novo Clearance to Medtronic’s GI Genius Model
    Contract Pharma

    Latest Breaking News From Contract Pharma

    Bristol Myers Squibb Expands at Cambridge Crossing
    Amgen Completes Five Prime Acquisition
    Sartorius Expands in the UK
    Beauty Packaging

    Latest Breaking News From Beauty Packaging

    Former L’Oréal Exec Joins Glossier
    Lancôme Reveals New Global Sustainability Program
    First-Ever Skincare Line Focuses on Iron To Prevent Aging
    Happi

    Latest Breaking News From Happi

    Fragrance Creators Association Celebrates P&G Executive
    Evonik Highlights Solutions for Malodor Reduction
    P&G Emphasizes Small Actions at Home To Be More Sustainable
    Ink World

    Latest Breaking News From Ink World

    Kumon North America Adds Speedmaster XL 106 from Heidelberg
    SE-DA Invests in Kornit Presto S
    Acrylic Resins Market Worth $21.9 Billion by 2025: MarketsandMarkets
    Label & Narrow Web

    Latest Breaking News From Label & Narrow Web

    TLMI reveals Eugene Singer Award winners at Virtual Spring Summit
    Monadnock Paper Mills joins SGP
    ACTEGA helps converter reach sustainability goals
    Nonwovens Industry

    Latest Breaking News From Nonwovens Industry

    Albaad to Add Natural-Based Line in Israel
    First Quality to Discontinue Tampon Operations
    Jessup Installs New Era Coating and Laminating Line
    Orthopedic Design & Technology

    Latest Breaking News From Orthopedic Design & Technology

    BioMagnetic Sciences Names President and CEO
    Mainstay Medical Launches ReActiv8 in Australia
    Biogennix Rolls Out Agilon Strip Bone Graft
    Printed Electronics Now

    Latest Breaking News From Printed Electronics Now

    Virtual ASMC 2021 Spotlights Advanced Semiconductor Manufacturing Excellence
    LG Display Cuts Down CO2-eq Emissions by 3 Million Tons in 2020
    European Commission's Innovation Radar Acknowledges 3 ARMOR Innovations

    Copyright © 2021 Rodman Media. All rights reserved. Use of this constitutes acceptance of our privacy policy The material on this site may not be reproduced, distributed, transmitted, or otherwise used, except with the prior written permission of Rodman Media.

    AD BLOCKER DETECTED

    Our website is made possible by displaying online advertisements to our visitors.
    Please consider supporting us by disabling your ad blocker.


    FREE SUBSCRIPTION Already a subscriber? Login